title: Interventions to improve chronic cyclosporine A nephrotoxicity through inhibiting renal cell apoptosis: a systematic review.
abstract: OBJECTIVE
  To reveal interventions for chronic cyclosporine A nephrotoxicity (CCN) and provide new targets for further studies, we analyzed all relevant studies about interventions in renal cell apoptosis.
  
  
  METHODS
  We collected all relevant studies about interventions for cyclosporine A (CsA)-induced renal cell apoptosis in Medline (1966 to July 2010), Embase (1980 to July 2010) and ISI (1986 to July 2010), evaluated their quality, extracted data following PICOS principles and synthesized the data.
  
  
  METHODS
  We included all relevant studies about interventions in CsA-induced renal cell apoptosis no limitation of research design and language) and excluded the duplicated articles, meeting abstracts and reviews without specific data.
  
  
  RESULTS
  There were three kinds of intervention, include anti-oxidant (sulfated polysaccharides, tea polyphenols, apigenin, curcumin, spirulina, etc), biologics (recombinant human erythropoietin (rhEPO), a murine pan-specific transforming growth factor (TGF)-beta-neutralizing monoclonal antibody1D11, cartilage oligomeric matrix protein (COMP)-angiopoietin-1 and hepatocyte growth factor (HGF) gene), and other drugs (spironolactone, rosiglitazone, pirfenidone and colchicine). These interventions significantly improved the CCN, renal cell apoptosis and renal dysfunction through intervening in four apoptotic pathways in animals or protected renal cells from apoptosis induced by CsA and increased cell survival through respectively four pathways in vitro.
  
  
  CONCLUSIONS
  There are three group interventions for CCN. Especially anti-oxidant drugs can significantly improve CCN, renal cell apoptosis and renal dysfunction. Many drugs can improve CCN through intervening in Fas/Fas ligand or mitochondrial pathway with sufficient evidences. Angiotensin II, nitric oxide (NO) and endoplasmic reticulum (ER) pathways will be new targets for CCN.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Ministry Health of China, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Cheng-wen
authors.initials: CW
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Shan
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Sheng-fu
authors.initials: SF
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.forename: You-ping
authors.initials: YP
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002908:Chronic Disease; D016572:Cyclosporine / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008928:Mitochondria / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology
chemical_list: D007166:Immunosuppressive Agents; D019014:fas Receptor; D009569:Nitric Oxide; D016572:Cyclosporine